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Ageing is the major risk factor for idiopathic PARKINSONS DISEASE (PD), the first motor neurodegenerative disorder (in EU 1% in 65\; about 4% in 80\). The most recent conceptualizations of ageing and PD indicate that they share basic mechanisms, e.g. accumulation of senescent cells and propagation phenomena such as inflammaging mirrored in PD by neuro-inflammaging in brain that foster a prion-like spreading of neuronal damage. Thus, to fully understand PD pathogenesis and set up innovative neuro-protective therapies it is mandatory to posit PD within the framework of ageing process. The main goal of PROPAG-AGEING is to identify specific cellular and molecular perturbations deviating from healthy ageing trajectories towards PD. To this aim the project will exploit four large, very informative EXISTING COHORTS where biomaterials are available: i) de novo PD patients (before any therapy) followed longitudinally, including the largest repository of PD patients, i.e. PPMI; ii) centenarians and their offspring (CO) who never showed clinical signs of motor disability; iii) old twins of the Swedish Twin Registry (STR) followed longitudinally for >45 years, assessed for lifestyle and exposure to toxicants, and where incident and prevalent cases of PD discordant twins have been collected, including brains. The most informative sample from these cohorts will be studied in a DISCOVERY PHASE by an integrated set of omics to identify molecular signatures whose results will enter in a VALIDATION PHASE exploiting the four large cohorts, and performing functional in in vitro studies using dopaminergic neurons obtained by PD somatic cells from PD patients and centenarians via iPSC protocol. An added value is that omic data in centenarians and CO are available, and will represent the gold standard of healthy ageing. This approach will allow to identify new molecular profiles for early diagnosis and therapy (identification of druggable targets) of PD and signatures of healthy ageing.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 7.62M | Year: 2012

Hematological diseases are highly heterogeneous malignancies in the matter of the molecular mechanisms related to their development and progression. A considerable heterogeneity can be further observed within the same hematological disease at the inter-individual level, being reflected by different clinical outcomes and responses to treatment in different patients. Nowadays, the advent of high-throughput next generation sequencing (NGS) technologies that are revolutionizing genomics and transcriptomics by providing a single base resolution tool for a unified deep analysis of diseases complexity allows a fast and cost-efficient fine-scale assessment of the genetic variability hidden within cohorts of patients affected by the same leukemia. That being so, by potentially highlighting inter-individual differences that may play a role in the differential success of diverse therapeutic interventions, they promise to be crucial for selecting the most appropriate medical treatments. This project aims at developing a European Hematological/NGS platform of scientists for improving outcomes for therapeutic interventions on acute and chronic leukemias and at developing strategies to personalize treatments and tailor therapies to different stratified groups of leukemia patients, with the goal of optimizing their efficacy and safety through a deeper and deeper understanding of the influence of genetic alterations on leukemias pathogenesis and treatment response (i.e. personalized therapy). Moreover, the final aim will be the identification of novel prognostic biomarkers for acute and chronic leukemias, as well as of molecular biomarkers and/or genome-wide profiles for the assessment of minimal residual disease. The originality of this project is to perform systematic deep whole exome/transcriptome studies on well-clinically-characterized leukemia patients, by exploiting NGS technologies able to quickly produce data with a good cost-effectiveness and an unprecedented resolution.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 2.87M | Year: 2016

Life expectancy is increasing dramatically, but the period of good health (healthspan) enjoyed by most is not keeping pace, with implications for health, social care, and pensions resulting in estimated costs more than doubling by 2050. Thus, understanding the many factors that contribute to healthy ageing versus frailty, and validating interventions and influencing policy to promote healthy ageing is a cross-cutting research priority in Europe. Given the considerable impact of lifestyle factors on healthy ageing and disease, there is a surprising lack of innovative multi-disciplinary training and research examining the influence of physical activity and nutrition on age-related changes at gene to societal level. PANINI will address this gap by coordinating research laboratories across Europe to focus on cutting-edge ageing and health research through training 11 ESRs across scientific disciplines to create a holistic approach to the challenge of ageing in the 21st Century. PANINI is a European Training Network with 8 world-leading beneficiaries working on Healthy Ageing and 10 non-academic partners carefully selected for quality and range of sectors. These vary in size including 1 large nutrition company, 5 SMEs, 2 charities, 1 healthcare partnership and 1 EU Joint Research Centre. PANINIs vision is to implement multidisciplinary cross-sectoral research and training of a new cohort of researchers taking a radically innovative approach to overcome the challenge of unhealthy ageing. The main goals of PANINI are to: integrate expertise from basic biomedical science and technology to applied clinical practice; standardise measurements across the network to create a toolkit and shared dataset; provide multidisciplinary training secondments to expose ESRs to healthcare and industry research settings and other laboratories; disseminate widely the shared and individual project findings; and use these to develop a policy document to promote healthy ageing in Europe.

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